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Schizophrenia begins in the womb, study suggests

Researchers may be one step closer to determining the cause of schizophrenia, after uncovering an abnormal genetic process associated with the disease that begins in the womb.

Researchers have uncovered a schizophrenia-related process that begins in the womb.

By transforming skin cells from patients with schizophrenia into neuronal progenitor cells - cells that form neurons in early development - researchers identified an abnormal gene pathway called nuclear FGFR1 (nFGFR1) that impairs early brain development.

Senior study author Michal K. Stachowiak, Ph.D., of the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo in New York, and colleagues say that their findings may bring us closer to treatments that could prevent schizophrenia in utero.

The researchers recently reported their results in the journal Schizophrenia Research.

According to the National Institute of Mental Health, around 1.1 percent of adults in the United States have schizophrenia - a mental health disorder characterized by hallucinations, delusions, and abnormal thoughts.

While the exact causes of schizophrenia remain unclear, researchers have long known that the condition can run in families, suggesting a genetic origin. Furthermore, an increasing number of studies have uncovered genetic mutations associated with an increased risk of schizophrenia.

For their study, Stachowiak and colleagues sought to learn more about the genomic processes that occur in utero that might influence the risk of schizophrenia development.

Dysregulated nFGFR1 pathway impairs brain development

To reach their findings, the researchers collected skin cells from four adults with schizophrenia and four adults without the disorder.

The skin cells were reprogrammed into induced pluripotent stem cells, and these differentiated into neuronal progenitor cells. This enabled the team to assess the processes that occur during early brain development in people with schizophrenia.

The researchers pinpointed a dysregulated nFGFR1 pathway that targets and mutates numerous genes associated with schizophrenia. The team explains that just one of these gene mutations can impact brain development.

According to the authors, these findings provide proof of concept that schizophrenia may be caused by a dysregulated genomic pathway that influences the brain before birth.

"In the last 10 years, genetic investigations into schizophrenia have been plagued by an ever-increasing number of mutations found in patients with the disease. We show for the first time that there is, indeed, a common, dysregulated gene pathway at work here."

Michal K. Stachowiak, Ph.D.

Furthermore, the team says that these findings open the door to new schizophrenia treatments. For example, a drug could be administered to expectant mothers, whose offspring has a high risk of developing schizophrenia, that prevents processes related to the disease occurring in the developing fetus.

In future studies, the researchers plan to grow "mini brains" using the same processes used in the current study, with the aim of gaining a deeper understanding of how dysregulation of the nFGFR1 pathway influences early brain development, as well as to provide a model to test possible treatments.

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